Ruthenium-based metathesis catalysts, precursors for their preparation and their use

ABSTRACT

The invention is directed to ruthenium-based metathesis catalysts of the Grubbs-Hoveyda type. The new 2-aryloxy-substituted ruthenium catalysts described herein reveal rapid initiation behavior. Further, the corresponding styrene-based precursor compounds are disclosed. The catalysts are prepared in a cross-metathesis reaction starting from styrene-based precursors which can be prepared in a cost-effective manner. 
     The new Grubbs-Hoveyda type catalysts are suitable to catalyze ring-closing metathesis (RCM), cross metathesis (CM) and ring-opening metathesis polymerization (ROMP). Low catalyst loadings are necessary to convert a wide range of substrates including more complex and critical substrates via metathesis reactions at low to moderate temperatures in high yields within short reaction times.

The present invention is directed to ruthenium-based metathesiscatalysts, which are of the Grubbs-Hoveyda type. The new2-aryloxy-substituted O-chelating Ru-based catalysts described hereinallow rapid metathesis reactions even at mild reaction conditions suchas at low temperatures and short reaction times. They reveal a rapidinitiation behavior.

In a further aspect, the invention is directed to new styrene-basedprecursors, which are intermediate products for the preparation of theruthenium-based catalysts of the present invention. These styrene-basedprecursors can be prepared in a cost- and time-effective manner andallow for an economic and straightforward preparation of the newmetathesis catalysts described herein.

The invention further provides a method for producing the newruthenium-based catalysts starting from the styrene-based precursors andalso relates to the use of the new Ru-based catalysts for olefinmetathesis. The method according to the present invention ischaracterized by few reaction steps and allows for the synthesis of theRu-based catalysts with excellent yields. Thus the method is suitable tobe adopted directly to synthesize the catalysts according to the presentinvention in a commercial production scale.

The Ru-based catalysts are especially suitable to catalyze ring-closingmetathesis (RCM), cross metathesis (CM) and ring-opening metathesispolymerization (ROMP). The new catalysts combine fast catalystinitiation with exceptional activity in olefin metathesis reactions. Lowcatalyst loadings are sufficient to convert a wide range of substratesvia metathesis reactions.

Ru-based catalysts for olefin metathesis reactions are known from theprior art and have gained more and more importance over the past decade.Generally, the olefin metathesis reaction comprises a metal-catalyzedrearrangement of carbon-carbon double bonds and is especially importantin the production of complex natural products and polymers. However,such reactions tend to be limited by its initiation rate. Consequently,fast olefin metathesis transformation requires elevated temperatures orrapidly initiating precatalysts.

Ru-based catalysts are particularly suited for catalyzing suchreactions. This is due to their high stability and wide tolerance towardvarious functional groups. Since their first introduction, thesecatalysts have been enhanced in their stability and reactivity byvarious alterations of the respective ligands. The Hoveyda-Grubbs typecatalysts known from the prior art are typically characterized by a2-isopropoxy-group at a benzylidene ligand (ref to formula (a)). Theoxygen atom is bound to the ruthenium atom in a chelating manner.

The respective metathesis catalyst has been described in WO 02/14376 A2.A catalyst loading of about 1 mol-% to 5 mol-%, moderate to highreaction temperatures and reaction times of up to 44 hours werenecessary for obtaining a sufficient yield of RCM reaction productdepending on the respective substrates.

In a later development, modifications have been made on the benzylidenegroup by introducing electron-withdrawing and electron-donating groups(Y, Z) at the 4- and 5-position of the six-membered ring which has animpact on the Ru═CHR bond as well (see formula (b)).

Such modified metathesis catalysts have been prepared by Lemcoff, Tzuret al. It is mentioned that the catalysts show activity for ring-closingmetathesis and cross metathesis. Respective experimental data revealedsufficient yields of the respective reaction products with catalystloadings of between 1 mol-% and 2.5 mol-%. Lower yields were obtainedwhen using the cited catalysts in more challenging metathesis reactionssuch as cross metathesis (ref. to Tzur, E., Szadkowska, A., Ben-Asuly,A., Makal, A., Goldberg, I., Wozniak, K., Grela, K., Lemcoff, N. G.,Chem. Eur. J. 2010, 16, 8726-8737).

Furthermore, various olefin metathesis catalysts have also been reportedby Lemcoff et al., suggesting nitrogen, sulfur, selenium and phosphorusas chelating atoms (ref. to Diesendruck, C. E., Tzur, E., Ben-Asuly, A.,Goldberg, I., Straub, B. F., Lemcoff, N. G., Inorg. Chem. 2009, 48,10819-10825). Grela et al. have reported pyridine-based rutheniumcatalysts bearing a chelating nitrogen atom. Ruthenium catalystscontaining an amine chelating ligand have also been reported by Grela etal. (ref. to Zukowska, K., Szadkowska, A., Pazio, A. E., Wozniak, K.,Grela, K., Organometallics 2012, 31, 462-469). High temperatures, longreaction times of several hours up to several days as well as moderateto high catalyst loading were necessary for obtaining sufficient yieldof the respective metathesis reaction products.

N-chelated Grubbs-Hoveyda type catalysts have also been provided byPlenio, Peeck et al. (ref to formula (c) and (d)). However, thepreparation of the N-chelated catalysts is expensive and time-consumingespecially due to fact that the precursors can only be obtained by alaborious and expensive preparation method comprising several reactionsteps (ref. to Peek, L. H., Savka, R. D., Plenio, H., Chem. Eur. J.2012, 18, 12845-12853).

In summary, the ruthenium-based catalysts known from the prior art havethe drawback of slow initiation rates requiring elevated reactiontemperatures and/or demanding a moderate to high catalyst loading forobtaining a sufficient yield of a metathesis reaction product. Thus,catalysts known from the prior art usually have low to moderateactivity. Further, as outlined above, the catalysts (c) and (d),recently described by Peek, Savka and Plenio require laborious andexpensive preparation steps.

It is one object of the present invention to overcome the drawbacks ofthe metathesis catalysts known from the prior art. Thus, stable andrapidly initiating Ru-based catalysts, which are of the Grubbs-Hoveydatype and suitable for metathesis reactions, are provided in the presentinvention. It is a further object of the present invention to providecatalysts, which enable high substrate conversion rates in metathesisreactions even with sterically demanding substrates, such as in RCM withtri-substituted olefinic substrates.

Further, new styrene-based precursors are presented, which are suitablefor the synthesis of the Ru-based catalysts of the present invention andwhich can usually be prepared cost-effectively with high yield in a fewreaction steps starting from commercially available raw materials. Stillfurther, the invention also provides a method which allows acost-effective production of the new Ru-based catalysts with high yieldsstarting from the corresponding styrene-based precursors reportedherein. The new catalysts should be suitable to catalyze olefinmetathesis reactions with high yields even at low catalyst loadings. Thecatalysts should also be capable of catalyzing olefin metathesisreactions under low to moderate temperatures within short reactiontimes. Thus, the catalysts should possess an increased catalyticactivity compared to the activity of catalysts known from the art. Thecatalyst should be suitable to catalyze different types of olefinmetathesis reactions of a broad range of various substrates. Finally,the Hoveyda-Grubbs type catalysts should allow for metathesis reactionsunder standard inert techniques such as Schlenk techniques without theneed of special precautions.

The objects of the invention are solved by the subject-matter of theclaims. The object is especially solved by the provision of new Ru-basedcatalysts of the Grubbs-Hoveyda type and by the provision ofstyrene-based precursors for their preparation.

The catalysts are obtainable starting from the styrene-based precursorsaccording to the present invention by a cross metathesis reaction withRu-based starting complexes in a single-reaction step.

The styrene-based precursors for producing the new Ru-based catalysts ofthe present invention are characterized by formula (I)

wherein

-   -   a, b, c and d are, independently from each other, selected from        hydrogen, straight chain or branched alkyl groups including        C₁-C₁₀-alkyl, C₁-C₁₀-alkoxy, C₁-C₁₀-alkylthio, C₁-C₁₀-silyloxy,        C₁-C₁₀-alkylamino, optionally substituted C₆-C₁₄-aryl,        optionally substituted C₆-C₁₄-aryloxy, optionally substituted        C₆-C₁₄-heteroaryl or electron-withdrawing groups (EWG);    -   R¹ is selected from hydrogen, straight chain or branched alkyl        groups including C₁-C₁₀-alkyl, C₁-C₁₀-alkoxy, C₁-C₁₀-alkylthio,        C₁-C₁₀-silyloxy, C₁-C₁₀-alkylamino, C₁-C₁₀-dialkylamino,        C₆-C₁₄-aryl, C₆-C₁₄-aryloxy, C₆-C₁₄-heterocyclic or        electron-withdrawing groups (EWG), and    -   R² is selected from hydrogen, straight chain or branched        C₁-C₁₀-alkyl groups.

EWGs are atoms or functional groups that withdraw electron density fromneighboring atoms. Suitable EWGs according to the present invention areselected from halogen atoms, trifluormethyl (—CF₃), nitro (—NO₂),sulfinyl (—SO—), sulfonyl (—SO₂—), formyl (—CHO), C₁-C₁₀-carbonyl,C₁-C₁₀-carboxyl, C₁-C₁₀-alkylamido, C₁-C₁₀-aminocarbonyl, nitrile (—CN)or C₁-C₁₀-sulfonamide groups.

R¹ in formula (I) is preferably selected from straight chain or branchedalkyl groups including C₁-C₁₀-alkyl, C₁-C₁₀-alkoxy, C₁-C₁₀-alkylthio,C₁-C₁₀-silyloxy, C₁-C₁₀-alkylamino, C₁-C₁₀-dialkylamino, C₆-C₁₄-aryl,C₆-C₁₄-aryloxy, C₆-C₁₄-heterocyclic or electron-withdrawing groups(EWG). It is further preferred that R¹ in formula (I) is selected fromC₁-C₁₀-alkylamino, C₁-C₁₀-dialkylamino, halogen atoms or nitro (—NO₂).Most preferably, R¹ in formula (I) is selected from dimethylamino(—NMe₂), nitro (—NO₂) and chlorine (—Cl).

R² is selected from hydrogen or straight chain or branched C₁-C₁₀-alkylgroups. Preferably, R² is hydrogen, methyl, ethyl, n-propyl, iso-propyl,n-butyl or iso-butyl. In a most preferred version, R² is hydrogen ormethyl.

Preferably, a, b, c and d are, independently from each other, selectedfrom hydrogen, straight chain or branched alkyl groups includingC₁-C₁₀-alkyl, C₁-C₁₀-alkoxy or EWGs. In a preferred embodiment, a, b, cand d each are hydrogen.

According to a further preferred embodiment, the styrene-based precursorfor the preparation of the new Ru-based catalysts is characterized byformula (Ia):

According to an alternative embodiment, the styrene-based precursor ischaracterized by formula (Ib):

According to a further embodiment, the styrene-based precursor ischaracterized by formula (Ic):

In a further embodiment, the styrene-based precursor is characterized byformula (Id):

The styrene-based precursors of the present invention may be easilyobtained from the corresponding benzaldehyde intermediates via a singlestep reaction by nucleophilic substitution.

The conditions for the preparation of the benzaldehyde intermediates areexemplarily presented in the examples section. They can be obtainedcost-effectively with a yield of more than 60%. The benzaldehydeintermediates are, for example, obtained by stirring a mixturecomprising starting materials and a reaction solvent such as achlorinated hydrocarbon solvent, at a temperature in the range of 50° C.to 200° C. depending on the respective starting materials for a periodin the range of 1 to 12 hours. After stirring, the benzaldehydeintermediates are usually isolated and further purified by conventionalmethods.

The low-cost raw materials for producing the benzaldehyde intermediatesare commercially available and may comprise a 4-substituted phenol and2-fluorobenzaldehyde. Alternatively, the raw materials may comprise a4-substituted 1-fluoro-benzene and a 2-hydroxy benzaldehyde.

The inventive styrene-based precursors may be easily obtained from thebenzaldehyde intermediates by reaction with Wittig reagent via a singlestep reaction. The conditions for the reaction are exemplarily presentedin the examples section.

The Ru-based catalysts of the present invention are obtainable startingfrom the styrene-based precursors according to the present invention bya cross metathesis reaction with a Ru-based starting complex. TheRu-based catalysts described herein are especially suitable to catalyzeolefin metathesis reactions with a superior activity even at lowcatalyst loadings and low to moderate temperatures.

The Ru-based catalysts of the present invention are characterized inthat two aryl groups are directly bonded to the chelating oxygen atom,i.e. the Ru-based catalysts are 2-aryloxy-substituted Grubbs-Hoveydatype catalysts. The aryl group of the 2-aryloxy-substituent ischaracterized in that it has one substituent which is in para positionwith respect to the attached oxygen atom. This unexpectedly allows forsuperior catalytic activity and fast initiation rates of the Ru-basedcatalysts. The Ru-based catalysts of the present invention are describedby formula (II):

wherein

-   -   L is a neutral two-electron donor ligand;    -   a, b, c and d are, independently from each other, selected from        hydrogen, straight chain or branched alkyl groups including        C₁-C₁₀-alkyl, C₁-C₁₀-alkoxy, C₁-C₁₀-alkylthio, C₁-C₁₀-silyloxy,        C₁-C₁₀-alkylamino, optionally substituted C₆-C₁₄-aryl,        optionally substituted C₆-C₁₄-aryloxy, optionally substituted        C₆-C₁₄-heteroaryl or electron-withdrawing groups (EWG);    -   R¹ is selected from hydrogen, straight chain or branched alkyl        groups including C₁-C₁₀-alkyl, C₁-C₁₀-alkoxy, C₁-C₁₀-alkylthio,        C₁-C₁₀-silyloxy, C₁-C₁₀-alkylamino, C₁-C₁₀-dialkylamino,        C₆-C₁₄-aryl, C₆-C₁₄-aryloxy, C₆-C₁₄-heterocyclic or        electron-withdrawing groups (EWG);    -   X is an anionic ligand independently selected from the group of        halogen anions (i.e. chloride, bromide or iodide),        tetrafluoroborate (BF₄ ⁻) or acetate (CH₃COO⁻).

In this formula, L represents a neutral two-electron donor ligand.Generally, the neutral two-electron donor ligand is selected from thegroup of phosphine ligands and the group of N-heterocyclic carbeneligands (NHC ligands). Preferably, the neutral two-electron donor ligandis selected from the group of N-hetero-cyclic carbene ligands (NHCligands).

The phosphine ligands may be selected from the group of alkylphosphinessuch as tri-iso-propylphosphine, tricyclohexylphosphine (PCy₃) andtricyclopentylphosphine. Further, the phosphine ligand may be aphospha-bicycloalkane compound such as 9-phosphabicyclo-[3.3.1]-nonaneor 9-phosphabicyclo-[4.2.1]-nonane (also named “phobanes”). Preferably,the phospha-bicycloalkane compound is selected from the group of9-cyclohexyl-9-phospha-bicyclo-[3.3.1]-nonane (“cyclohexylphobane”),9-(2,2,4-trimethylpentyl)-9-phospha-bicyclo-[3.3.1]-nonane(2,2,4-trimethylpentyl “phobane”) and9-isobutyl-9-phospha-bicyclo-[3.3.1]-nonane (“isobutylphobane”).

In a preferred embodiment, L is an N-heterocyclic carbene ligand (NHCligand). According to the present invention, NHC ligands areN-containing heterocycles comprising stable singlet carbenes that act asexcellent two electron donor ligands towards ruthenium. The NHC ligandcomprises at least one nitrogen atom and carbon atoms as ring atoms. Atleast one nitrogen ring atom is bound to a further moiety which is notpart of the heterocyclic ring structure. The NHC ligand preferablycomprises at least two nitrogen atoms as ring atoms and may be saturatedor unsaturated.

The NHC ligand is preferably selected from formula (III) or (IV):

In formula (III) and (IV), R³ is a substituted aryl group selected from2,4,6-trimethylphenyl (“mesityl”), 2,6-di-isopropylphenyl,3,5-di-tert.-butylphenyl and 2-methylphenyl and combinations thereof.

Preferably, the NHC ligand is selected from the group of1,3-bis-(2,4,6-trimethylphenyl)-imidazolidine-2-ylidene (“SIMes”),1,3-bis-(2,6-di-isopropylphenyl)imidazolidine-2-ylidene (“SIPr”) or1,3-bis-(2,6-di-isopropylphenyl)-imidazoline-2-ylidene (unsaturated NHC,“IPr”).

X is an anionic ligand, preferably from the group of halogen anions suchas chloride, bromide or iodide; in a most preferred embodiment, X isCl⁻.

The groups a, b, c and d and the EWG substituents are defined asdescribed above for the styrene-based precursor of formula (I).

R¹ in formula (II) is preferably selected from hydrogen,C₁-C₁₀-alkylamino, C₁-C₁₀-dialkylamino, halogen atoms or nitro (—NO₂).Most preferably, R¹ in formula (II) is selected from hydrogen,dimethylamino (—NMe₂), nitro (—NO₂) and chlorine (—Cl).

Preferably, a, b, c and d are, independently from each other, selectedfrom hydrogen, straight chain or branched alkyl groups includingC₁-C₁₀-alkyl, C₁-C₁₀-alkoxy or electron-withdrawing groups (EWG). In afurther preferred embodiment, a, b, c and d each are hydrogen. In casea, b, c and d are each hydrogen, Ru-based catalysts having superiorcatalytic activity are obtained. In such catalysts, the Ru—O bond isprimarily influenced.

In a specific embodiment, the Ru-based catalyst according to the presentinvention is characterized by formula (IIa):

In a further specific embodiment, the Ru-based catalyst of the presentinvention is characterized by formula (IIb):

In further specific embodiments, the inventive Ru-based catalyst ischaracterized by formula (IIc) or formula (IId):

In further alternative embodiments, the provided Ru-based catalyst ischaracterized by one of formulas (IIe), (IIf), (IIg) or (IIh),preferably by formula (IIe) or by formula (IIf):

In addition to the Ru-based catalysts described above, the presentinvention also refers to a method for manufacturing these new Ru-basedcatalysts. Generally, the present catalysts are obtainable from the newstyrene-based precursors of formula (I) via a single-step reaction. Asingle step reaction according to the present invention is a reactionthat precedes without necessitating intermediate isolation orintermediate purification steps (hereinafter called “one-potsynthesis”).

A variety of Ru-based starting complexes of the general formulaL₂X₂Ru═CR_(x)R_(y)(wherein R_(x) and R_(y) may be independentlyhydrogen, alkyl or aryl and wherein R_(x) and R_(y) may form a ring) canbe employed as starting material for the preparation of the catalysts ofthe present invention. Examples of suitable Ru-based starting complexesare the well-known Ru-benzylidene complexes of Grubbs 1^(st) generation(containing phosphine ligands) or the Grubbs 2^(nd) generationRu-complexes (containing NHC ligands).

In a preferred method of the invention, the styrene-based precursor offormula (I) is reacted with a Ru-based starting complex of formula (V)in a cross metathesis reaction to yield the Ru-based catalysts offormula (II). This reaction is shown in Scheme 1.

In the Ru-based starting complex of formula (V), L may be a phosphineligand selected from the group of tri-isopropylphosphine,tricyclohexylphosphine (PCy₃), tricyclopentylphosphine andphospha-bicycloalkane compounds such as9-cyclohexyl-9-phospha-bicyclo-[3.3.1]-nonane (“cyclohexylphobane”),9-(2,2,4-trimethylpentyl)-9-phospha-bicyclo-[3.3.1]-nonane(2,2,4-trimethylpentyl phobane”) and9-isobutyl-9-phospha-bicyclo-[3.3.1]-nonane (“isobutylphobane”).

In a preferred version of the method, L is a NHC ligand selected fromthe group of 1,3-bis-(2,4,6-trimethylphenyl)-imidazolidine-2-ylidene(“SIMes”), 1,3-bis-(2,6-diisopropylphenyl)-imidazolidine-2-ylidene(“SIPr”) or 1,3-bis-(2,6-di-isopropylphenyl)imidazoline-2-ylidene(unsaturated NHC, “IPr”).

Further, in the Ru-based starting complex of formula (V) above, L′ is aleaving ligand representing a phosphine ligand selected from the groupof triisopropylphosphine, tricyclohexylphosphine (PCy₃),tricyclopentylphosphine, 9-cyclohexyl-9-phospha-bicyclo-[3.3.1]-nonane(“cyclohexylphobane”),9-(2,2,4-trimethylpentyl)-9-phospha-bicyclo-[3.3.1]-nonane(2,2,4-trimethylpentyl phobane”),9-isobutyl-9-phospha-bicyclo-[3.3.1]-nonane (“isobutylphobane”) or apyridine ligand, which may be substituted or unsubstituted. Examples arepyridine or bromopyridine. In a most preferred embodiment, L′ ispyridine.

X is an anionic ligand, preferably from the group of halogen anions suchas chloride, bromide or iodide; in a most preferred embodiment, X ischloride (Cl⁻).

Preferably, the method of preparing the Ru-based catalysts according tothe present invention comprises the following reaction steps:

-   a) providing a reaction mixture, which comprises the styrene-based    precursor of formula (I), the Ru-based starting complex of    formula (V) and a reaction solvent;-   b) optionally stirring the mixture;-   c) evaporating the reaction solvent;-   d) optionally purifying the remaining reaction product.

Preferably, the molar ratio of the styrene-based precursor of formula(I) to the Ru-based starting complex of formula (V) is at least 1.00 andmore preferably at least 1.01, further preferred at least 1.05. In casethis molar ratio is too low, the inventive catalysts cannot be obtainedwith a high yield. The molar ratio of the styrene-based precursor offormula (I) to the Ru-based starting complex of formula (V) should notexceed a value of 1.5; preferably the molar ratio should not exceed avalue of 1.2.

It is particularly preferred that the molar ratio of the styrene-basedprecursor of formula (I) to the Ru-based starting complex of formula (V)is between 1.05 and 1.15.

Depending on the Ru-based starting complex of formula (V) used, thereaction conditions for the cross metathesis reaction may be modified;in particular, the reaction mixture of reaction step a) may furthercomprise Cu-salts (such as CuCl or CuBr) as phosphine scavengers whenusing phosphine containing Ru-starting complexes such as, for example,(PCy₃)₂Cl₂Ru-phenylindenylidene. It should be noted, however, that theaddition of Cu-salts is not necessary, if the leaving ligand L′ is not aphosphine.

It is preferred that the reaction mixture of reaction step a) furthercomprises an acidic ion exchange resin, preferably in case the leavingligand L′ is a pyridine or tricyclohexylphosphine ligand. The preferredpresence of the resin surprisingly allows for improved yields of theinventive catalysts. It is assumed that this facilitates thesubstitution of the leaving ligand L′ by the inventive styrene-basedprecursor. Preferably, the resin is based on functionalized styrenedivinylbenzene copolymers. The functional group is preferably of thesulphuric acid type. More preferably, the resin comprises Amberlyst®resin; most preferably, the resin is Amberlyst® resin. Suitable ionexchange resins are disclosed in WO 2011/091980 A1.

The reaction mixture comprises a reaction solvent, preferably achlorinated hydrocarbon solvent such as dichloromethane (DCM),chloroform or 1,2-dichloroethane (DCE) or in cyclic ethers such astetrahydrofuran (THF) or dioxane. Alternatively, aromatic hydrocarbonsolvents such as benzene or toluene as well as esters and mixtures ofthe listed solvents may be employed. Most preferably, the reactionsolvent is selected from DCM and THF.

The suitable reaction time for step b) depends on the type of thestarting materials. Typically, the mixture is stirred in the range offrom 0.25 to 2 hours, preferably 0.25 to 1.5 hours and most preferably0.5 to 1 hour to complete the reaction. Reaction temperatures may varydepending on the raw materials during stirring. Typically, reactiontemperatures in the range of up to 100° C., preferably up to 80° C. areappropriate. More preferably, the reaction temperatures do not exceed50° C., especially preferably they do not exceed 45° C. The reaction ispreferably carried out under an inert gas such as nitrogen or argon,most preferably argon.

Optionally, the resin is separated by filtration following reaction stepb). Subsequent to reaction step b) or optionally after subsequentfiltration of the acidic ion exchange resin, the reaction solvent isremoved, preferably in vacuo. The remaining reaction product may befurther purified. This is preferably done by washing the reactionproduct with a suitable solvent. Suitable solvents include aliphaticalcohols, alkanes, alkenes and mixtures thereof. Preferably, the solventis selected from methanol, n-pentane or mixtures thereof. Furtherpurification steps may be conducted.

The Ru-based catalysts according to the present invention are obtainablefrom the precursors of formula (I) by the described method within shortreaction times under mild to moderate reaction conditions. This ensuresa cost-effective and time-saving preparation route resulting in improvedmetathesis catalysts with high purity in high yield. Preferably, theRu-based catalysts are obtainable by the described method in yields ofat least 60%, more preferably at least 65% and most preferably at least70%.

The Ru-based catalysts according to the present invention may be used tocatalyze metathesis reactions with a wide range of substrates. Asalready described, these catalysts are particularly suitable to catalyzering-closing metathesis (RCM), cross metathesis (CM), ring-openingmetathesis polymerization (ROMP) and other metathesis reactions. Ingeneral, metathesis reactions are performed in homogenous phase.Alternatively, the reaction may be carried out in a heterogeneous mannerwith immobilized or supported catalysts; for example in the presence ofcation-exchange resins. The reaction conditions for the metathesisreactions are well known to a person skilled in the art. The reaction iscarried out in a suitable reaction solvent, which may be, for example,1, 2-dichloroethane, hexafluorobenzene or toluene. Preferably thereaction solvent comprises toluene. Most preferably the reaction solventis toluene. Preferably, the metathesis reaction is conducted under aprotective inert gas such as nitrogen or argon, preferably argon.

The Ru-based catalysts of the present invention allow for reactiontemperatures during metathesis reaction below 60° C., preferably below55° C. Such low temperatures are important when employingtemperature-sensitive substrate materials. Moreover, the catalystsaccording to the present invention also allow for excellent yields ofreaction products even at temperatures about 0° C. This is evident fromFIG. 1 and FIG. 2.

Further, the Ru-catalysts of the present invention enable exceptionallow catalyst loadings. Preferably, the catalyst loading is below 1.000ppm, i.e. below 0.1 mol-%. Further preferably, catalyst loadings of notmore than 250 ppm, more preferably of not more than 100 ppm aresufficient for obtaining high conversions. Thus, the metathesisreactions can be conducted in a cost-effective manner.

The Ru-catalysts of the present invention allow for metathesis reactionswith short reaction times. Typically, as shown in the experimentalsection, more than 60% of the substrate is converted after 15 minutes.This is measured by known methods, preferably by gas chromatography(GC). In most cases a conversion of ≥70% and preferably of ≥75% isobtained with the Ru-based catalysts of the present invention after areaction time of at least 15 minutes under the conditions mentionedabove. In various metathesis reactions, the conversion reaches 90% oreven 99% after 15 minutes reaction time. In some cases, a yield ofisolated finished product of >80%, more preferably ≥90% can be obtained.

The Ru-based catalysts of the present invention show a fast initiationrate and thus translate into fast and efficient olefin metathesisreactions while having an excellent catalytic activity even at low tomoderate reaction temperatures. A TON (“Turn-over number”; i.e. molarratio of converted substrate to catalyst) of preferably >3×10³, furtherpreferred ≥5×10³ and still further preferred ≥8×10³ and especiallypreferred of ≥3×10⁴ may be obtained with the inventive new Ru-basedcatalysts. The TOF (TON per hour; turn-over frequency) which is ameasure for the catalytic activity preferably amounts up to >1×10⁴ h⁻¹,further preferred ≥2×10⁴ h⁻¹ and most preferred ≥7×10⁴ h⁻¹. In specificembodiments, a TOF of ≥1×10⁵ h⁻¹ is obtained.

It was found by the present inventors, that it is necessary to providethe right balance between the steric and electronic effects of thesubstituents bonded to the chelating oxygen atom in order to tailor theactivity of the catalysts of the present invention. Thus it is supposedthat the excellent activity of the Ru-based catalysts compared to theruthenium-based catalysts of formula (a) may result from a modificationin the nature of the O-donor, i.e. from decreased donor properties ofthe oxygen atom as well as from lower steric interferences. Thismodification in the nature of the O-donor atom in the benzylidene ligandmay contribute to a weakening of the Ru—O interaction, a higherRu—O-distance and consequently lead to a significant increase in theinitiation rate of the catalyst. It is assumed that this contributes tothe fast and efficient metathesis reactions by using the new Ru-basedcatalysts. Up to date, such 2-phenoxy substituted Ru-catalysts have notbeen described in the literature.

In summary, the new Ru-based catalysts of the present invention combinefast catalyst initiation and high stability with exceptional activity inolefin metathesis reactions. Low catalyst loadings are sufficient forobtaining excellent yields of metathesis reaction products even withinshort reaction times and at low to moderate reaction temperatures. Thenew catalysts are easily obtainable with high purity and high yield in aone-step reaction from new styrene-based precursors. The styrene-basedprecursors are generally obtained with high yield from commercial rawmaterials in a cost-effective manner. Thus the new Ru-based catalystscan be manufactured economically in industrial scale.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows the conversion (in %) of N,N-diallyltosylamide (0.1 mol/L)during RCM reaction over a reaction period of 210 minutes at 0° C. intoluene using 0.025 mol-% (250 ppm) of catalysts of formulas (a), (IIb)and (IIf).

FIG. 2 shows the conversion (in %) of N,N-diallyltosylamide (0.1 mol/L)during RCM reaction over a reaction period of 20 minutes at 0° C. intoluene using 0.025 mol-% (250 ppm) of catalysts of formulas (IIb) and(IIf).

FIG. 3 shows an ORTEP plot of the crystal structure of catalyst (IIb).Important bond lengths (pm) and angles (°) are (two independentmolecules of catalyst (IIb) are observed in solid state, which differwith respect to the orientation of the phenyl group relative to the restof the molecule, the first number corresponds to molecule 1 followed bythe respective data for molecule 2): Ru—O 226.6(4), 230.5(3); Ru—C(NHC)198.4(5), 197.0(6); Ru═CHR 182.1(5), 180.9(5), Ru—Cl 230.7(2), 232.3(2),232.1(2), 234.0(2); Cl—Ru—Cl 153.71(6), 158.31(6). The significantvariability of the Ru—O distances in the two observed molecules ofcatalyst (IIb) indicates that there is a shallow energy potential curvefor the Ru—O bond and, thus, an increased sensibility of the bond withregard to minor disturbances.

FIG. 4 shows the absorbance-time curve of catalyst (IId) (1×10⁻⁴ mol/L)during reaction with butyl vinyl ether (0.01 M) in toluene at 30° C. Thedata are fitted using (y=A1·exp(−x/t₁)+y0) and (k_(obs)=1/t₁). Theabsorbance of catalyst (IId) probably resulting from theligand-metal-charge transfer (LMCT band) is measured at 370 nm. A fastdecrease of the absorbance of catalyst (IId) was observed. Thedissociation reaction required less than 20 seconds, even at a very lowconcentration of butyl vinyl ether (0.01 mol/L) and at a temperature,which was slightly above ambient temperature (30° C.). From this it isevident that the Ru—O bond is broken rapidly in the presence of theolefin.

The invention is further described by the following examples withoutlimiting or narrowing the scope of protection.

EXAMPLES General Remarks

All chemicals are purchased as reagent grade from commercial suppliersand used without further purification, unless otherwise noted. Allreactions involving ruthenium complexes are performed under anatmosphere of argon. CH₂Cl₂ (99.5%) and pentane (99%) are obtained fromGruessing GmbH, toluene from Sigma-Aldrich (Lab. Reagent grade, 99.3%).These solvents are dried and degassed by using a column purificationsystem. In this system, the solvents are sparged and pressurized withargon (0.1 to 1 bar), followed by successive passing through a columnfilled with activated alumina and a second column, either filled with asupported copper catalyst (pentane) or again activated alumina (CH₂Cl₂).Dimethylformamide is refluxed over calcium hydride and distilled underargon atmosphere. Tetrahydrofuran is dried over sodium and distilledunder argon atmosphere. All solvents are stored over molecular sieves (4Å).

¹H and ¹³C nuclear magnetic resonance spectra are recorded with a BrukerDRX300 spectrometer. The chemical shifts are given in parts per million(ppm) on the delta scale (δ) and are referenced to tetramethylsilane(¹H-, ¹³C-NMR=0.0 ppm) or the residual peak of CHCl3 (¹H-NMR=7.26 ppm,¹³C-NMR=77.16 ppm). Abbreviations for NMR data: s=singlet; d=doublet;t=triplet; q=quartet; sep=septet; m=multiplet; bs=broad signal.Preparative chromatography is performed using Merck silica 60(0.063-0.02 mesh). GC experiments are run on a Clarus 500 GC withautosampler and FID detector. Column: Varian CP-SiI 8 CB (I=15 m,d_(i)=0.25 mm, d_(F)=1.0 Im), N₂ (flow: 17 cm s⁻¹; split 1:50);Injector-temperature: 270° C., detector temperature: 350° C.

Example 1 Preparation of the Styrene-Based Precursors (Ia) to (Id)

The preparation is carried out starting from 4-substituted phenols (forpreparing styrene-based precursors of formula (Ia) to (Ic)) or startingfrom 4-substituted 1-fluoro-benzene for preparing styrene-basedprecursor of formula (Id). In the first reaction step, the respectivebenzaldehyde intermediates are prepared. The benzaldehyde intermediatesare then converted to the respective precursor (Ia) to (Id) in a secondreaction step.

a) Preparation of 2-(4-(dimethylamino)phenoxy)benzaldehyde,2-phenoxybenzaldehyde and 2-(4-chlorophenoxy)benzaldehyde

The benzaldehyde intermediates are synthesized following literatureprocedures with modifications. Into a dry Schlenk flask under argonatmosphere the corresponding phenol (17.7 mmol), 2-fluorobenzaldehyde(2.0 g, 16.1 mmol), potassium carbonate (5.6 g, 40.3 mmol) and anhydrousDMF (40 mL) are added at room temperature. The mixture is warmed in asealed flask to 170° C. and stirred at this temperature for 2 h (forpreparing 2-phenoxy-benzaldehyde and 2-(4-chlorophenoxy)benzaldehyde) orat 150° C. for 1.5 h (for preparing2-(4-(dimethylamino)phenoxy)benzaldehyde). Then the mixture is allowedto cool to room temperature and is treated with water (200 mL) and theproduct is extracted with diethyl ether (3×50 mL). The combined organiclayers are washed with NaOH (1M, 50 mL), brine (150 mL), dried overanhydrous MgSO₄ and evaporated in vacuum. The residue is purified bycolumn chromatography (cyclohexane/ethyl acetate 10:1, v/v (forpreparing 2-phenoxy-benzaldehyde and 2-(4-chlorophenoxy)benzaldehyde) orused in next reaction without purification (in case of2-(4-(dimethylamino)phenoxy)-benzaldehyde).

2-(4-(dimethylamino)phenoxy)benzaldehyde is obtained as a white solid(3.07 g, 79% yield). ¹H NMR (300 MHz, CDCl₃) δ 10.59 (d, J=0.8 Hz, 1H),7.90 (dd, J=7.8, 1.8 Hz, 1H), 7.44 (ddd, J=8.5, 7.3, 1.8 Hz, 1H),7.12-7.05 (m, 1H), 7.03-6.97 (m, 2H), 6.84-6.74 (m, 3H), 2.96 (s, 6H).

¹³C NMR (75 MHz, CDCl₃) b 189.85, 161.75, 148.14, 145.47, 135.76,128.33, 126.05, 122.23, 121.25, 116.90, 114.18, 41.34.

2-phenoxybenzaldehyde is obtained as a yellow oil (2.52 g, 79% yield).¹H NMR (300 MHz, CDCl₃) b 10.52 (d, J=0.8 Hz, 1H), 7.94 (dd, J=7.8, 1.8Hz, 1H), 7.51 (ddd, J=8.4, 7.3, 1.8 Hz, 1H), 7.43-7.35 (m, 2H),7.22-7.15 (m, 2H), 7.10-7.04 (m, 2H), 6.90 (dd, J=8.4, 0.8 Hz, 1H). ¹³CNMR (75 MHz, CDCl₃) b 189.45, 160.10, 156.53, 135.85, 130.22, 128.55,127.03, 124.44, 123.44, 119.51, 118.60.

2-(4-chlorophenoxy)benzaldehyde is obtained as a yellow solid (3.07 g,82% yield). ¹H NMR (500 MHz, CDCl₃) δ 10.48 (d, J=0.7 Hz, 1H), 7.94 (dd,J=7.8, 1.8 Hz, 1H), 7.53 (ddd, J=8.4, 7.3, 1.8 Hz, 1H), 7.37-7.33 (m,2H), 7.24-7.19 (m, 1H), 7.03-6.99 (m, 2H), 6.89 (dd, J=8.4, 0.7 Hz, 1H).¹³C NMR (126 MHz, CDCl₃) b 189.14, 159.62, 155.20, 135.95, 130.26,129.65, 128.85, 127.13, 123.91, 120.72, 118.60.

b) Synthesis of 2-(4-nitrophenoxy)benzaldehyde

Into a dry Schlenk flask under argon atmosphere are added1-fluoro-4-nitrobenzene (2.0 g, 14.2 mmol), salicylic aldehyde (2.1 g,17.0 mmol), potassium carbonate (4.9 g, 35.5 mmol) and anhydrous DMF (40mL). The mixture is warmed in a sealed flask to 100° C. and stirred atthis temperature overnight. Then the mixture is allowed to cool to roomtemperature, treated with water (200 mL) and the product is extractedwith diethyl ether (3×50 mL). Combined organic layers are washed withNaOH (1M in water, 50 mL) and brine (150 mL), dried over anhydrous MgSO₄and evaporated in vacuo. Residue is purified by column chromatography(cyclohexane/ethyl acetate 4:1, v/v).

2-(4-nitrophenoxy)benzaldehyde is obtained as a yellow solid (2.40 g,69% yield). ¹H NMR (300 MHz, CDCl₃) δ 10.34 (d, J=0.7 Hz, 1H), 8.28-8.23(m, 2H), 8.00 (dd, J=7.8, 1.8 Hz, 1H), 7.66 (dd, J=8.3, 7.4, 1.8 Hz,1H), 7.41-7.35 (m, 1H), 7.13-7.06 (m, 3H).

¹³C NMR (75 MHz, CDCl₃) δ 188.36, 162.64, 157.14, 143.61, 136.26,129.71, 128.14, 126.31, 125.85, 120.93, 117.87. HRMS: m/z calcd forC₁₃H₉NO₄ 243.0542; found: 243.0531. Analysis calcd. for C₁₃H₉NO₄(243.05): C 64.18, H 3.73, N 5.76; found: C 64.23, H 3.72, N 5.88.

c) Vinylation of the benzaldehyde intermediates

A Schlenk flask containing methyltriphenylphosphonium iodide (3.0 g,7.42 mmol) is evacuated and back-filled with argon three times.Anhydrous tetrahydrofuran (50 mL) is added by syringe and the formedsuspension is cooled to −10° C. KOtBu (902 mg, 8.04 mmol) is added inportions to the stirred mixture under a stream of argon, and stirringcontinued at −10° C. for 20 minutes. Subsequently, one of thebenzaldehyde intermediates (6.18 mmol) is added. The mixture is allowedto warm to room temperature, stirred overnight and poured into water(500 mL). The product is extracted with diethyl ether (3×100 mL). Theorganic phases are combined, washed with brine and dried over magnesiumsulfate. The solvent is removed in vacuo and the residue is purified bycolumn chromatography (cyclohexane/ethyl acetate 20:1, v/v).

Precursor (Ia) is obtained as a colorless solid (1.18 g, 80% yield). ¹HNMR (300 MHz, CDCl₃) δ 7.58 (dd, J=7.7, 1.8 Hz, 1H), 7.20-7.01 (m, 3H),6.96-6.89 (m, 2H), 6.80 (dd, J=8.2, 1.2 Hz, 1H), 6.76 (d, J=9.0 Hz, 2H),5.82 (dd, J=17.7, 1.4 Hz, 1H), 5.30 (dd, J=11.1, 1.4 Hz, 1H), 2.93 (s,6H). ¹³C NMR (75 MHz, CDCl₃) δ 155.69, 147.37, 131.49, 128.89, 128.66,126.61, 122.78, 120.11, 117.92, 115.02, 114.34, 41.51. HRMS: m/z calcdfor C₁₆H₁₇NO 239.1304; found: 239.1310. Analysis calcd. for C₁₆H₁₇NO(239.13): C 80.30, H 7.16, N 5.85; found C 79.88, H 7.11, N 5.83.

Precursor (Ib) is obtained as a colorless solid (0.99 g, 82% yield). ¹HNMR (500 MHz, CDCl₃) δ 7.62 (dd, J=7.8, 1.7 Hz, 1H), 7.34-7.30 (m, 2H),7.24 (dd, 1H), 7.16-7.13 (m, 1H), 7.07 (tt, J=7.6, 1.1 Hz, 1H), 7.01(dd, J=17.7, 11.1 Hz, 1H), 6.97-6.94 (m, 2H), 6.92 (dd, J=8.1, 1.1 Hz,1H), 5.81 (dd, J=17.7, 1.3 Hz, 1H), 5.29 (dd, J=11.1, 1.3 Hz, 1H).

¹³C NMR (75 MHz, CDCl₃) δ 158.05, 153.75, 131.12, 129.97, 129.83,129.14, 126.77, 124.21, 122.81, 120.23, 117.91, 115.51. Elementalanalysis calcd. for C₁₄H₁₂O (196.09) C 85.68, H 6.16; found C 85.49, H6.11.

Precursor (Ic) is obtained as a colorless liquid (1.20 g, 84% yield). ¹HNMR (300 MHz, CDCl₃) δ 7.60 (dd, J=7.7, 1.8 Hz, 1H), 7.28-7.20 (m, 3H),7.18-7.12 (m, 1H), 6.99-6.87 (m, 2H), 6.87-6.82 (m, 2H), 5.78 (dd,J=17.7, 1.3 Hz, 1H), 5.27 (dd, J=11.1, 1.2 Hz, 1H). ¹³C NMR (75 MHz,CDCl₃) δ 156.76, 153.32, 130.85, 130.07, 129.79, 129.26, 127.77, 126.93,124.66, 120.33, 118.97, 115.86. HRMS: m/z calcd for C₁₄H₁₁ClO 230.0494;found 230.04815. Elemental analysis calcd. for C₁₄H₁₁ClO (230.69): C72.89, H 4.81; found C 72.82, H 4.92.

Precursor (Id) is obtained as a yellow solid (1.15 g, 77% yield). ¹H NMR(300 MHz, CDCl₃) δ 8.22-8.16 (m, 2H), 7.68-7.64 (m, 2H), 7.38-7.24 (m,1H), 7.04-7.00 (m, 1H), 6.97-6.91 (m, 2H), 6.79 (dd, J=17.7, 11.1 Hz,1H), 5.79 (dd, J=17.7, 1.1 Hz, 1H), 5.29 (dd, J=11.1, 1.1 Hz, 1H). ¹³CNMR (75 MHz, CDCl₃) δ 163.61, 151.47, 142.67, 130.74, 130.20, 129.65,127.31, 126.21, 126.14, 121.73, 116.81, 116.51. HRMS: m/z calcd forC₁₄H₁₁NO₃ 241.0739; found: 241.0714 Elemental analysis calcd. forC₁₄H₁₁NO₃ (241.25) C 69.70, H 4.60, N 5.81; found C 69.93, H 4.68, N5.69.

Example 2

a) Preparation of catalysts (IIa) to (IIc) and (IIe) to (IIh)

A flame-dried Schlenk tube containing[RuCl₂(SIMes)(3-phenylindeneylidene)(py)](200 mg, 0.27 mmol; Umicore AG& Co. KG, Hanau, Germany) (for preparing catalysts (IIa) to (IIc)) or[RuCl₂(SIPr)(3-phenylindeneylidene)(py)] (200 mg, 0.24 mmol; Umicore AG& Co. KG, Hanau, Germany) (for preparing catalysts (IIe) to (IIh)) isevacuated and back-filled with argon three times. Methylene chloride (4mL), the respective styrene-based precursor (0.30 mmol for preparingcatalysts (IIa) to (IIc) or 0.26 mmol for preparing catalysts (IIe) to(IIh)) and Amberlyst resin (275 mg for preparing catalysts (IIa) to(IIc) or 250 mg for preparing catalysts (IIe) to (IIh), dry form, 4.70mmol H⁺/g) are added under an atmosphere of argon. The mixture isstirred at 40° C. for 30 minutes for preparing catalysts (IIa) to (IIc)or 60 minutes for preparing catalysts (IIf) to (IIh) or at roomtemperature for 1 h for preparing catalyst (IIe) and then filtered, toseparate the resin. The filtrate is evaporated in vacuo and theremaining solid is treated with pentane (10 mL) and the resultingsuspension is kept in an ultrasonic bath for 1 min. Solid residue isfiltered, washed with methanol (5 mL) and pentane (10 mL) and dried invacuo.

Catalyst (IIa) is obtained as a green solid (135 mg, 71% yield). ¹H NMR(500 MHz, CDCl₃) δ 16.71 (s, 1H), 7.37 (t, J=7.5 Hz, 1H), 7.13 (d, J=8.3Hz, 2H), 7.03 (s, 4H), 7.00-6.88 (m, 3H), 6.61 (d, J=8.0 Hz, 3H), 4.15(s, 4H), 2.93 (s, 6H), 2.47 (s, 12H), 2.37 (s, 6H). ¹³C NMR (126 MHz,CDCl₃) δ 292.65, 210.50, 154.24, 143.89, 138.79, 136.22, 129.54, 129.46,128.74, 127.69, 123.66, 122.90, 122.53, 113.86, 113.13, 51.81, 41.20,21.24, 19.43. HRMS: m/z calcd for C₃₆H₄₁N₃O₄Cl₂Ru 703.16809; found:703.1661.

Catalyst (IIb) is obtained as a green solid (142 mg, 80% yield). ¹H NMR(300 MHz, CDCl₃): δ 16.71 (d, J=0.9 Hz, 1H), 7.44-7.36 (m, 1H),7.25-7.14 (m, 5H), 7.03 (s, 4H), 7.00 (d, J=1.8 Hz, 1H), 6.94 (td,J=7.5, 0.8 Hz, 1H), 6.66 (d, J=8.3 Hz, 1H), 4.16 (s, 4H), 2.46 (s, 12H),2.37 (s, 6H). ¹³C NMR (75 MHz, CDCl₃) δ 292.53, 210.04, 153.24, 153.04,144.21, 138.85, 136.03, 129.52, 129.44, 126.03, 124.21, 122.82, 122.08,51.79, 21.22, 19.44. HRMS: m/z calcd for C₃₄H₃₆N₂OCl₂Ru 660.1253; found:660.1239.

Catalyst (IIc) is obtained as a green solid (129 mg, 69% yield). ¹H NMR(500 MHz, CDCl₃) b 16.70 (s, 1H), 7.42 (t, J=7.1 Hz, 1H), 7.24-7.18 (m,4H), 7.06-6.94 (m, 6H), 6.65 (d, J=8.1 Hz, 1H), 4.16 (s, 4H), 2.45 (s,12H), 2.38 (s, 6H). ¹³C NMR (75 MHz, CDCl₃) δ 292.09, 209.55, 152.61,151.71, 144.10, 138.98, 138.83, 135.94, 131.40, 129.55, 124.60, 123.43,122.96, 114.00, 51.80, 21.23, 19.41. HRMS: m/z calcd for C₃₄H₃₅N₂OCl₃Ru694.0820; found: 694.0845.

Catalyst (IIe) is obtained as a green solid (139 mg, 73% yield). ¹H NMR(500 MHz, CDCl₃) δ 16.59 (s, 1H), 7.49 (t, J=7.6 Hz, 2H), 7.32 (d, J=7.6Hz, 5H), 7.22 (d, J=8.1 Hz, 2H), 6.95-6.83 (m, 2H), 6.64-6.52 (m, 3H),4.13 (s, 4H), 3.64 (sep, J=6.2 Hz, 4H), 2.92 (s, 6H), 1.27 (d, J=6.7 Hz,12H), 1.19 (d, J=6.4 Hz, 12H). ¹³C NMR (126 MHz, CDCl₃) δ 287.86,213.42, 148.85, 142.88, 137.25, 129.67, 129.33, 124.67, 123.74, 123.46,121.94, 113.73, 113.04, 54.77, 41.10, 28.70, 26.49, 24.07. HRMS: m/zcalcd for C₄₂H₅₃N₃OCl₂Ru 787.2567; found: 787.2600. Elemental analysiscalcd. for C₄₂H₅₃N₃OCl₂Ru (787.88): C 64.03, H 6.78, N 5.33; found C64.56, H 6.96, N 5.12.

Catalyst (IIf) is obtained as a green solid (151 mg, 84% yield). ¹H NMR(500 MHz, CDCl₃) δ 16.59 (d, J=0.5 Hz, 1H), 7.49 (t, J=7.7 Hz, 2H),7.39-7.24 (m, 9H), 7.23-7.18 (m, 1H), 6.95 (dd, J=7.6, 1.6 Hz, 1H), 6.89(t, J=7.4 Hz, 1H), 6.56 (d, J=8.3 Hz, 1H), 4.14 (s, 4H), 3.63 (sep,J=6.7 Hz, 4H), 1.27 (d, J=6.9 Hz, 12H), 1.17 (d, J=6.6 Hz, 12H). ¹³C NMR(126 MHz, CDCl₃) δ 287.38, 212.79, 154.03, 153.04, 148.87, 143.08,137.11, 129.74, 129.50, 129.33, 126.46, 124.66, 123.93, 123.16, 122.19,113.85, 54.76, 28.71, 26.51, 23.97. HRMS: m/z calcd for C₄₀H₄₈N₂OCl₂Ru744.2185; found: 744.2178.

Catalyst (IIg) is obtained as a green solid (141 mg, 75% yield). ¹H NMR(500 MHz, CDCl₃) δ 16.57 (s, 1H), 7.50 (t, J=7.7 Hz, 2H), 7.39-7.35 (m,1H), 7.34-7.29 (m, 6H), 7.26-7.23 (m, 2H), 7.00-6.88 (m, 2H), 6.55 (d,J=8.3 Hz, 1H), 4.15 (s, 4H), 3.61 (sep, J=6.8 Hz, 4H), 1.27 (d, J=6.9Hz, 12H), 1.18 (d, J=6.6 Hz, 12H). ¹³C NMR (126 MHz, CDCl₃) δ 286.85,212.24, 153.61, 151.49, 148.85, 142.93, 137.00, 131.91, 129.82, 129.62,129.37, 124.69, 124.51, 124.32, 122.34, 113.69, 54.76, 28.73, 26.49,23.97. HRMS: m/z calcd for C₄₀H₄₇N₂OCl₃Ru 778.17584; found: 778.1784.Elemental analysis calcd. for C₄₀H₄₇N₂OCl₃Ru (778.80) C 61.63, H 6.08, N3.60; found 61.19, H 6.16, N 3.68.

Catalyst (IIh) is obtained as a green solid (125 mg, 66% yield). ¹H NMR(500 MHz, CDCl₃) δ 16.55 (s, 1H), 8.18-8.14 (m, 2H), 7.53-7.47 (m, 4H),7.45-7.40 (m, 1H), 7.33 (d, J=7.7 Hz, 4H), 7.00-6.98 (m, 2H), 6.63 (d,J=8.3 Hz, 1H), 4.16 (s, 4H), 3.57 (sep, J=6.7 Hz, 4H), 1.27 (d, J=6.9Hz, 12H), 1.17 (d, J=6.6 Hz, 12H). ¹³C NMR (126 MHz, CDCl₃) δ 285.70,211.08, 157.97, 152.17, 148.89, 145.60, 143.22, 136.77, 129.97, 129.39,126.16, 125.35, 124.71, 123.29, 122.80, 116.78, 114.27, 54.77, 28.79,26.51, 23.89. HRMS: m/z calcd for C₄₀H₇₄N₃O₃Cl₂Ru 789.2032; found:789.2029.

a) Preparation of Catalyst (IId)

A flame-dried Schlenk tube containing[RuCl₂(SIMes)(3-phenylindeneylidene) (py)](200 mg, 0.27 mmol; Umicore AG& Co. KG, Hanau, Germany) is evacuated and back-filled with argon threetimes. Tetrahydrofuran (5 mL) is added and the resulting suspension iscooled to 0° C. Then styrene-based precursor (Id) (65.7 mg, 0.27 mmol)and Amberlyst resin (275 mg, dry form, 4.70 mmol H⁺/g) is added and themixture is stirred at −5° C. for 30 minutes, filtered and evaporated invacuo. The solid residue is washed with methanol (5 mL), pentane (10 mL)and dried in vacuo.

Catalyst (IId) is obtained as a green solid (141 mg, 75% yield). ¹H NMR(500 MHz, CDCl₃) δ 16.69 (s, 1H), 8.12 (d, J=7.2 Hz, 2H), 7.49 (s, 1H),7.35 (d, J=7.4 Hz, 2H), 7.04 (s, 6H), 6.79 (d, J=7.3 Hz, 1H), 4.18 (s,4H), 2.43 (s, 12H), 2.40 (s, 6H). ¹³C NMR (126 MHz, CDCl₃) δ 291.42,208.52, 158.38, 150.86, 145.17, 144.58, 139.16, 138.94, 129.59, 129.46,125.78, 125.30, 123.47, 121.80, 114.94, 51.79, 21.28, 19.43.

Example 3 Catalyst Testing

The new Ru-based catalysts are exemplarily evaluated in ring-closingmetathesis reactions (RCM). Furthermore, the activity is compared with aconventional catalyst known from the prior art, i.e. catalysts offormulas (a), (c) and (d).

Results of RCM

Catalysts of formulas (IIa) to (IIh) are systematically tested for anumber of ring closing metathesis reactions leading to N-heterocycles. Acomparison with prior art catalyst (a) is made.

The ring-closing reactions are carried out in toluene at 50° C. with areaction time of 15 min. The substrate is present in an amount of 0.5mol/L. Reactions are carried out in sealed 10 mL Schlenk tubes under anatmosphere of argon. In a 10 mL Schlenk tube, substrate is dissolved indry toluene under an atmosphere of argon. This solution is heated to 50°C. and catalyst (0.0025 to 0.02 mol-%) (25 to 200 ppm) from a stocksolution (0.75 mmol/L) in toluene is added. The latter is prepared byadding 4.0·10⁻⁶ mol of catalyst (IIa) to (IIh) into a 10 mL Schlenktube, evacuating the tube, filing the tube with argon and subsequentaddition of 5.34 mL of dried toluene under a stream of argon. TheSchlenk tube is kept in an ultrasonic bath for 1 min for completedissolution of the inventive catalyst.

The substrate concentration is defined as c(S)=n(S)/(V(S)+V(toluene)+V(stock solution)). For the determination of substrate conversion,samples (10 μL, substrate conc. 0.5 M) are taken after the specifiedtimes under a stream of argon and injected into GC vials containing 250μL of a 25% (v/v) ethyl vinyl ether solution in toluene. The conversionsare determined by GC. The degree of conversions is the averageconversion of two runs. The results are presented in Table 1.

The catalysts according to the present invention allow for excellentsubstrate conversions of ≥60% within less than 15 minutes of reactiontime at a low catalyst loading of between and at low to moderatetemperatures. For the majority of RCM substrates a conversion of evenabout 90% or higher within 15 minutes of reaction time is measured.

In this context, the new Ru-based catalysts of the present inventionseem to be especially efficient in RCM reactions leading to di- ortri-substituted cyclic olefins (ref to Table 1, entry 6 and Table 2).

TABLE 1 Conversion (in %) in RCM reactions of various substrates forcatalysts of the invention (IIa to IIh) and prior art catalyst (a) atdifferent catalyst loadings Catalyst loading Conversion (%) EntrySubstrate [ppm] (a) IIa IIb IIc IId IIe IIf IIg IIh 1

 25 70 83 90 73 83 99 — 81 99 2

 15 — — 74 64 — 91 96 78 92 3

 50 60 71 60 — 54 89 91 — 83 4

 50 — — 91 — 80 — 98 — — 5

200 — 92 92 — 77 99 99 — 98 6

 50 39 — 61 — — 90 72 — 84 Reaction conditions: Toluene solvent, 0.5Msubstrate, T = 50° C., reaction time 15 minutes, conversions detected byGC, average of two runs.

Apart from the low catalyst loading, the short reaction time requiredfor such reactions is most notable—all of the reactions studied arealmost completed within less than 15 min.

TON and TOF are calculated for substrate of entry no. 4 and catalyst(IIf). Accordingly, by using catalyst (IIf) a TON of 6.4×10⁴ and a TOFof 2.56×10⁵ h⁻¹ is observed. This is a significant improvement withrespect to the prior art.

Catalyst of formula (IIb) is tested under the above mentioned conditionsfor a ring closing metathesis reaction with a more complicated andcritical substituted olefinic substrate in comparison with N-chelatedGrubbs-Hoveyda-type catalysts of formulas (c) and (d) known from theprior art.

TABLE 2 Conversion (in %) in RCM reactions for catalyst (IIb) of theinvention and prior art catalysts (c) and (d) Catalyst loadingConversion (%) Substrate [ppm] (c) (d) IIb

50 58 54 78 Reaction conditions: Toluene solvent, 0.5M substrate, T =50° C., reaction time 15 minutes, conversions detected by GC, average oftwo runs.Comparative Tests with Prior Art Catalysts

In the RCM of N,N-diallyltosylamide at 0° C. catalysts of formula (IIb)and (IIf) are significantly faster than the prior art catalyst (a). Atlow temperatures fast initiation translates into excellent catalyticactivities compared to catalyst (a) known from the art, which initiateconsiderably more slowly. FIG. 1 shows the results of the RCM reaction.After 120 min a complete conversion is almost obtained for catalysts(IIb) and (IIf), while it takes much longer for the less rapidlyinitiating catalyst (a). The faster activation of catalysts (IIb) and(IIf) is evident from the faster initial transformation of the substrateto the respective RCM product.

The fast initiation and substrate conversion is also evident from FIG.2, which gives a detailed view on the conversion (in %) ofN,N-diallyltosylamide within the first 20 minutes for catalysts (IIb)and (IIf). Accordingly, a conversion of more than 20% is obtained evenwithin 9 minutes at 0° C. Figure also shows that catalyst (IIb)initiates faster than catalyst (IIf).

The increased catalytic activity of the catalysts according to thepresent invention compared with prior art catalyst (a) is also confirmedin Table 1. According to Table 1, the catalysts of the present inventionshow a considerably higher activity in RCM reactions with differentsubstrates.

Furthermore, a strong influence of temperature on the catalystperformance is noted. In order to obtain about 85% yield in the RCM ofN,N-diallyltosylamide at 0° C., about 250 ppm of the catalyst of formula(IIf) are required at a reaction time of about 180 min. At 50° C. ayield of 96% is obtained within 15 min using only 15 ppm of the catalystof formula (IIf) (ref to Table 1).

Still further, from Table 2 it is evident that catalyst (IIb) enablessuperior conversion rates of important and more critical substrates suchas diethylallyl-(2-methylallyl)malonate compared with the N-chelatedcatalysts known from the prior art. Considering the more complicatedsynthesis of N-chelated catalysts as well as the stability of N-chelatedGrubbs-Hoveyda-type catalysts, which is usually limited, the Ru-basedcatalysts according to the present invention provide exceptionaladvantages in view of the catalysts already known.

1.-20. (canceled)
 21. A compound of formula (I) for the preparation ofruthenium-based catalysts

wherein a, b, c and d are, independently from each other, selected fromhydrogen, straight chain or branched alkyl groups includingC₁-C₁₀-alkyl, C₁-C₁₀-alkoxy, C₁-C₁₀-alkylthio, C₁-C₁₀-silyloxy,C₁-C₁₀-alkylamino, optionally substituted C₆-C₁₄-aryl, optionallysubstituted C₆-C₁₄-aryloxy, optionally substituted C₆-C₁₄-heteroaryl orelectron-withdrawing groups (EWG); R¹ is hydrogen, straight chain orbranched C₁-C₁₀-alkyl, C₁-C₁₀-alkoxy, C₁-C₁₀-alkylthio, C₁-C₁₀-silyloxy,C₁-C₁₀-alkylamino, C₁-C₁₀-dialkylamino, C₆-C₁₄-aryl, C₆-C₁₄-aryloxy,C₆-C₁₄-heterocyclic or electron-withdrawing groups (EWG); R² ishydrogen, straight chain or branched C₁-C₁₀-alkyl groups.
 22. Thecompound according to claim 21, wherein the electron-withdrawing groupsare halogen atoms, trifluormethyl (—CF₃), nitro (—NO₂), sulfinyl (—SO—),sulfonyl (—SO₂—), formyl (—CHO), C₁-C₁₀-carbonyl, C₁-C₁₀-carboxyl,C₁-C₁₀-alkylamido, C₁-C₁₀-aminocarbonyl, nitrile (—CN) orC₁-C₁₀-sulfonamide.
 23. The compound according to claim 21, wherein a,b, c and d each are hydrogen; R¹ is dimethylamino (NMe₂-), nitro (NO₂—)or chlorine (Cl); and R² is hydrogen, methyl, ethyl, n-propyl,iso-propyl, n-butyl or iso-butyl.
 24. The compound according to claim23, having the formula (Ia)


25. The compound according to claim 21, having the formula (Ib)


26. A ruthenium-based catalyst of formula (II)

wherein L is a neutral two-electron donor ligand, a, b, c and d are,independently from each other, selected from hydrogen, straight chain orbranched C₁-C₁₀-alkyl, C₁-C₁₀-alkoxy, C₁-C₁₀-alkylthio, C₁-C₁₀-silyloxy,C₁-C₁₀-alkylamino, optionally substituted C₆-C₁₄-aryl, optionallysubstituted C₆-C₁₄-aryloxy, optionally substituted C₆-C₁₄-heteroaryl orelectron-withdrawing groups (EWG); R¹ is hydrogen, straight chain orbranched alkyl groups including C₁-C₁₀-alkyl, C₁-C₁₀-alkoxy,C₁-C₁₀-alkylthio, C₁-C₁₀-silyloxy, C₁-C₁₀-alkylamino, C₆-C₁₄-aryl,C₆-C₁₄-aryloxy, C₆-C₁₄-heterocyclic or electron-withdrawing groups(EWG); X is an anionic ligand independently selected from the group ofhalogen anions (Cl⁻, Br⁻, I⁻), tetrafluoroborate (BF₄ ⁻) or acetate(CH₃COO⁻).
 27. The catalyst according to claim 26, wherein theelectron-withdrawing groups are halogen atoms, trifluormethyl (—CF₃),nitro (—NO₂), sulfinyl (—SO—), sulfonyl (—SO₂—), formyl (—CHO),C₁-C₁₀-carbonyl, C₁-C₁₀-carboxyl, C₁-C₁₀-alkylamido,C₁-C₁₀-aminocarbonyl, nitrile (—CN) or C₁-C₁₀-sulfonamide.
 28. Thecatalyst according to claim 26, wherein L is a N-heterocyclic carbene(NHC) ligand.
 29. The catalyst according to claim 26, wherein L is aN-heterocyclic carbene ligand having the formula (III) or (IV)

wherein R³ is selected from the group of 2,4,6-trimethylphenyl,2,6-di-isopropyl-phenyl, 3,5-di-tert.-butylphenyl, 2-methylphenyl andcombinations thereof.
 30. The catalyst according to claim 26, wherein Lis a NHC ligand selected from the group of1,3-bis-(2,4,6-trimethylphenyl)imidazolidine-2-ylidene (“SIMes”),1,3-bis-(2,6-di-isopropylphenyl)-imidazolidine-2-ylidene (“SIPr”) or1,3-bis-(2,6-di-isopropylphenyl)-imidazoline-2-ylidene (“IPr”); X isCl⁻; a, b, c and d each are hydrogen; R¹ is hydrogen, dimethylamino(NMe₂), nitro (NO₂) or chlorine (Cl).
 31. The catalyst according toclaim 26, wherein L is a phosphine ligand selected from the group oftri-isopropylphosphine, tricyclohexylphosphine (PCy₃),tricyclopentylphosphine and phospha-bicycloalkane compounds selectedfrom the group of 9-cyclohexyl-9-phosphabicyclo-[3.3.1]-nonane(“cyclohexylphobane”),9-(2,2,4-trimethylpentyl)-9-phosphabicyclo-[3.3.1]-nonane(“2,2,4-trimethylpentyl phobane”) and9-isobutyl-9-phospha-bicyclo[3.3.1]-nonane (“isobutylphobane”).
 32. Thecatalyst according to claim 30, having the formula (IIa)


33. The catalyst according to claim 30, having the formula (IId)


34. The catalyst according to claim 30, having the formula (IIe)


35. The catalyst according to claim 30, having the formula (IIh)


36. A method for preparing the catalyst according to claim 26,comprising reacting a compound of formula (I)

wherein a, b, c and d are, independently from each other, selected fromhydrogen, straight chain or branched alkyl groups includingC₁-C₁₀-alkyl, C₁-C₁₀-alkoxy, C₁-C₁₀-alkylthio, C₁-C₁₀-silyloxy,C₁-C₁₀-alkylamino, optionally substituted C₆-C₁₄-aryl, optionallysubstituted C₆-C₁₄-aryloxy, optionally substituted C₆-C₁₄-heteroaryl orelectron-withdrawing groups (EWG); R¹ is hydrogen, straight chain orbranched C₁-C₁₀-alkyl, C₁-C₁₀-alkoxy, C₁-C₁₀-alkylthio, C₁-C₁₀-silyloxy,C₁-C₁₀-alkylamino, C₁-C₁₀-dialkylamino, C₆-C₁₄-aryl, C₆-C₁₄-aryloxy,C₆-C₁₄-heterocyclic or electron-withdrawing groups (EWG); R² ishydrogen, straight chain or branched C₁-C₁₀-alkyl groups with aRu-starting compound having the formula (V):

in a cross metathesis reaction, wherein L is a phosphine ligand selectedfrom the group of tri-iso-propyl-phosphine, tricyclohexylphosphine(PCy₃), tricyclopentylphosphine, cyclohexylphobane,2,2,4-trimethylpentylphobane or isobutyl-phobane or a NHC ligandselected from the group of1,3-bis-(2,4,6-trimethylphenyl)-imidazolidine-2-ylidene (“SIMes”),1,3-bis-(2,6-di-isopropylphenyl)-imidazolidine-2-ylidene (“SIPr”) or1,3-bis-(2,6-diisopropylphenyl)-imidazoline-2-ylidene (“IPr”) and L′ isa leaving ligand from the group of tri-iso-propylphosphine,tricyclohexylphosphine (PCy₃), tricyclopentylphosphine,cyclo-hexylphobane, 2,2,4-trimethylpentyl-phobane, isobutylphobane orsubstituted or unsubstituted pyridine ligands; X is an anionic ligandselected from the group of halogen anions (Cl⁻, Br⁻, I⁻).
 37. The methodfor preparing the catalysts according to claim 36, wherein L is a NHCligand selected from the group of1,3-bis-(2,4,6-trimethylphenyl)imidazolidine-2-ylidene (“SIMes”),1,3-bis-(2,6-di-isopropylphenyl)-imidazolidine-2-ylidene (“SIPr”) or1,3-bis-(2,6-di-isopropylphenyl)-imidazoline-2-ylidene (“IPr”), L′ ispyridine, X is Cl⁻.
 38. An olefin metathesis reaction which comprisesutilizing the catalyst according to claim
 26. 39. The metathesisreaction as claimed in claim 38, wherein the reaction is a ring-closingmetathesis (RCM), cross metathesis (CM) or ring-opening metathesispolymerization (ROMP).
 40. The metathesis reaction as claimed in claim38, wherein the olefin metathesis is carried out at temperatures <55° C.with catalyst loadings <0.1 mol-%.
 41. The metathesis reaction asclaimed in claim 38, wherein reaction is a ring-closing metathesis(RCM), wherein the activity of the catalyst in the reaction (turn-overfrequency, TOF) is >1×10⁴ h⁻¹.